Animate
O,ONCaCBackbone
On the left you should see a black square containing an animated molecule.
Drag the molecule with your mouse -- you can watch the animation from
any perspective!

(To see the animation,
you must be using a compatible browser with Chime installed. For help,
close this window and click on the large Quick Start link near the
top of the FrontDoor -- it will
check your browser automatically and explain how to make it work.)

Animations
can illustrate several things, including:

"Morphed" conformational changes,
such as calcium binding to an EF Hand, seen on the left
(Note 1), or the
examples below including enzymes binding inhibitors.
These are morphs between two
empirically-determined conformations.

Animations of conformational changes show interpolations
or "morphs"
between two experimentally observed conformations. They help
the eye to relate the two conformations, but rarely if ever
do they attempt accurately to predict the true trajectory of
a reaction. The rationale and limitations of protein morphs are
summarized at the
Protein Morpher.

The "canned" animation, above left, can be rotated (by dragging
on it with your mouse), but
is limited to one rendering and color scheme.
When the animation is played in
Protein Explorer, you can view it in a variety
of renderings (secondary structure cartoon, ball and stick, spacefilling) and color
schemes. Also, the playback speed can be adjusted, or each frame can be viewed individually.

Once you
obtain an animation that can be played
in Protein Explorer, you can save the animation
window directly from Protein Explorer as HTML. It can then be played
back in Netscape (smoother animation) or Internet Explorer (jumpier animation)
without running Protein Explorer.
For example, here is such a saved animation HTML file
(press the Animate button to start animation)
for serotonin N-acetyltransferase
binding substrate.

Starting Animation in Protein Explorer

The links on this page
automatically start Protein Explorer at the
NMR Models/Animation page
(Note 2).
All you have to do is
wait for the green "Ready" indicator,
and press the [Animate] button.

Important - READ THIS

When loading ensembles of NMR models or morphs elsewhere,
Protein Explorer will likely default to starting at the FirstView page.
To start animation:

Scroll down to the bottom of the FirstView control panel,
and click on PE Site Map.

Here are links that show examples of morphs in Protein Explorer.
See the yellow box at left for instructions.

The
EF hand
shown on this page, binding calcium
(from recoverin).
Replace the default script in the box on Protein Explorer's NMR Models/Animation
page with this script,
and then press the [Animate] button.

Calmodulin binding peptide.
Caution: this is a linear interpolation. For a full explanation of
the limitations of linear interpolation and an introduction to recoverin,
see the Protein
Morpher.
Although calcium ions remain bound at all times, for technical reasons,
they are shown only in the two end states.
This morph includes only alpha carbons -- hence, trace, cartoon,
and secondary structure colors cannot be displayed. (1osa -> 2bbm.)

To see the position of the peptide throughout the morph,
insert the two commands below in the script box,
immediately before the line
"#--End color scheme--".

select :b
dots 20#--End color scheme--

Serotonin N-Acetyl transferase binding inhibitory substrate analog.
This enzyme catalyses the penultimate but rate-limiting step in melatonin
synthesis.
Caution: this is a linear interpolation. For a full explanation of
the limitations of linear interpolation and an introduction to recoverin,
see the Protein
Morpher.
This morph includes only alpha carbons -- hence, trace, cartoon,
and secondary structure colors cannot be displayed, but this speeds
up the animation considerably. Here is the
same animation with all sidechains (generated by the
Morph Server of Krebs and Gerstein).
(1b6b:a -> 1cjw:a)
To see the position of the substrate throughout the animation,
insert these two commands as instructed in the previous paragraph.

select ligand
dots 30

To highlight sidechains with dramatic movements, delete
the script in the box and paste
this script in, then press
Animate.

Staphylococcal accessory regulator A (SARA) binding DNA.
This is a transcriptional regulator controlling virulence
(Schumacher et al., 2001).
Caution: this is a linear interpolation. For a full explanation of
the limitations of linear interpolation and an introduction to recoverin,
see the Protein
Morpher.
This morph includes only alpha carbons -- hence, trace, cartoon,
and secondary structure colors cannot be displayed, but this speeds
up the animation considerably. Doing a morph with sidechains is problematic
because a homodimer is required, and each monomer contains gaps.
(1fzn dimer from PQS
-> 1fzp)
To see the position of the DNA throughout the animation,
insert the two commands below in the script box,
immediately before the line
"#--End color scheme--".

select dna,hetero
dots 30
#--End color scheme--

Lipase
(triacylglycerol hydrolase)
has been observed in both closed and open conformations
(Grochulski
et al., 1994).
This transition starts with the catalytic site "closed" and the
enzyme surface largely polar, so the protein is likely soluble.
A single loop moves to open access to the catalytic site,
leaving a hydrophobic pocket, presumably able to engage a substrate fat droplet.
Caution: this is a linear interpolation. For a full explanation of
the limitations of linear interpolation and an introduction to recoverin,
see the Protein
Morpher.
This morph includes only alpha carbons -- hence, trace, cartoon,
and secondary structure colors cannot be displayed, but this speeds
up the animation considerably.
(1trh -> 1lpm; thanks to Byron Rubin for acquainting me
with lipase.)
To see the position of the inhibitor (substrate analog)
throughout the animation,
insert the two commands below in the script box,
immediately before the line
"#--End color scheme--".

select mpa
dots
#--End color scheme--

Methods: In order to show an animation, Protein Explorer requires
a series of models (atomic coordinate sets), each representing
one frame in the animation. These must be provided in a PDB
file that distinguishes each model with MODEL [number] and ENDMDL
records, following the convention adopted for ensembles of models
resulting from
NMR experiments. Preparation of morphs is somewhat
technical; various
methods for morphing macromolecules
are described.
Simulations of Binding Processes

The process of
HIV protease inhibitor Ritonavir binding
to the protease has been simulated,
starting with
1HXW,
by pulling the
inhibitor out of the "side" of the protease with concurrent real-time
energy minimization by molecular mechanics using
MDL Sculpt.
This simulation is fictional, but chemically possible.
Here are four animations saved from Protein Explorer's
NMR/Animations page, emphasizing
backbone,
spacefill,
contacts, or
water.
You can also
view the animation in PE, where you can control the rendering
and color scheme. Here are the
scripts that produced the
renderings and colorings in the previous four saved animations.
Here is an alternative simulation in which the inhibitor was
pulled out the "top" of the protease, opening the "lid".

When ensembles of models resulting from
NMR experiments are
animated, they simulate thermal motion. Here are some examples.

Recoverin (1JSA), N-terminus flexible with covalently linked myristic acid.
To speed up the animation, this link shows only the alpha carbons,
but that precludes rendering as cartoon, trace, or spacefill.
Alternatively, being aware that it is a large file (1.1 megabytes),
here is the
ensemble of NMR models with all sidechains.

Calmodulin (1CFC),
calcium-free form, much flexibility.
To speed up the animation, this link shows only the alpha carbons,
but that precludes rendering as cartoon, trace, or spacefill.
Alternatively, being aware that it is a large file (1.1 megabytes),
here is the
ensemble of NMR models with all sidechains.

Calmodulin (2BBN),
calcium-bound form, little flexibility.
To speed up the animation, this link shows only the alpha carbons,
but that precludes rendering as cartoon, trace, or spacefill.
Alternatively, being aware that it is a large file (1 megabyte),
here is the
ensemble of NMR models with all sidechains.

Note 1: The animation shown on this page is a morph of one of two EF hands in recoverin,
namely residues 65-92. The interpolation is between model 7 of 1iku
and model 9 of 1jsa. (These models were chosen as being representative.)
The interpolation and energy minimization for the morph were
done by the
Morph Server
of
Gerstein & Krebs at Yale Univ
(see macromolecular morphing methods).
Further information about recoverin, and other morphs of it, are
available at the
Protein Morpher.